ZEB1 Axis Research Articles

Corrigendum: Long non-coding RNA HOTAIRM1 promotes proliferation and inhibits apoptosis of glioma cells by regulating the miR-873-5p/ZEB2 axis.

Corrigendum: Long non-coding RNA HOTAIRM1 promotes proliferation and inhibits apoptosis of glioma cells by regulating the miR-873-5p/ZEB2 axis.

Long Non-Coding RNA TMPO-AS1 Promotes Cervical Cancer Cell Proliferation, Migration, and Invasion by Regulating miR-143-3p/ZEB1 Axis.

ObjectiveLong non-coding RNAs (lncRNAs) have been identified as important players in tumorigenesis. LncRNA TMPO antisense RNA 1 (TMPO-AS1) has been shown to be involved in several tumors. However, the functional role and the underlying mechanism of TMPO-AS1 in regulating cervical cancer cell behavior remain unclear.Materials and MethodsExpression of TMPO-AS1, miR-143-3p, and ZEB1 were examined by qRT-PCR and Western blot. Cell proliferation, migration and invasion were evaluated using CCK-8 assay and Transwell migration and invasion assays, respectively. Luciferase reporter assay was performed to investigate the interaction miR-143-3p and TMPO-AS1 or ZEB1.ResultsTMPO-AS1 was highly expressed in cervical cancer cells. Furthermore, TMPO-AS1 overexpression significantly promoted C-33A cell proliferation, migration, and invasion. In contrast, TMPO-AS1 silencing inhibited SiHa cell proliferation, migration, and invasion. Mechanistically, TMPO-AS1 acted as a sponge of miR-143-3p to elevate expression of zinc finger E-box binding homeobox 1 (ZEB1), a target of miR-143-3p, and thereby promoted C-33A cell proliferation, migration, and invasion. Further assays showed that TMPO-AS1 knockdown inhibited cervical cancer cell tumorigenesis in vivo.ConclusionTMPO-AS1 promotes cervical cancer cell proliferation, migration, and invasion by regulating the miR-143-3p/ZEB1 axis.

The Lnc LINC00461/miR-30a-5p facilitates progression and malignancy in non-small cell lung cancer via regulating ZEB2

ABSTRACT Studies have found that Lnc LINC00461 is an important regulator of cancer. However, the function of Lnc LINC00461 in NSCLC is not known. Therefore, this experimental design was based on Lnc LINC00461 to explore the pathogenesis of Non-small cell lung cancer (NSCLC). RT-qPCR was used to detect the expression of lnc LINC00461 and miR-30a-5p in NSCLC. The CCK-8 method and Transwell assay were used to detect the effects of lnc LINC00461 and miR-30a-5p on proliferation, migration in NSCLC. Target gene prediction and screening, luciferase reporter assays were used to validate downstream target genes of lnc LINC00461 and miR-30a-5p. The protein expression of ZEB2 was detected by Western blot. The tumor changes in mice were detected by in vivo experiments. Lnc LINC00461 was significantly elevated in NSCLC. Lnc LINC00461 knockdown significantly inhibited proliferation and migration in NSCLC. miR-30a-5p was a direct target of lnc LINC00461 and miR-30a-5p was significantly reduced in NSCLC. shLINC00461 and miR-30a-5p inhibitor partially eliminated the effect of shLINC00461 on cell proliferation. And lnc LINC00461 was negatively correlated with miR-30a-5p expression. ZEB2 was a direct target of miR-30a-5p, and miR-30a-5p mimic and sh lnc LINC00461 significantly reduced ZEB2 expression levels. Finally, In vivo, lnc LINC00461 promoted tumor growth by modulating the miR-30a-5p / ZEB2 axis. In conclusion, LncLINC00461 promoted the progression of NSCLC by the miR-30a-5p / ZEB2 axis, and lnc LINC00461 may be a potential therapeutic target for NSCLC.

LncRNA TTN-AS1 facilitates proliferation, invasion, and epithelial-mesenchymal transition of breast cancer cells by regulating miR-139-5p/ZEB1 axis.

Breast cancer is a common malignant tumor suffered predominantly by women worldwide, which results in serious levels of morbidity and mortality. To control the effects of the cancer, it is critically important to elucidate the pathophysiological processes by which it occurs and develops. Reports have demonstrated that long noncoding RNAs perform a critical role in the development and metastasis of cancers. The lncRNA TTN-AS1 is considered carcinogenic. Nevertheless, the importance and biological functions of TTN-AS1 in breast cancer require greater exploration. In the current paper, we observed that TTN-AS1 expression was significantly upregulated in breast cancer tissues/cells compared with those that are healthy. TTN-AS1 enhanced the proliferation, migration, invasion, and epithelial-mesenchymal transformation of breast cancer cells. Furthermore, a direct target of TTN-AS1, miR-139-5p was negatively regulated. In addition, zinc finger E-box binding homeobox 1 (ZEB1) is an important nuclear transcription factor, the expression of which is increased in multiple tumors. Here, we also found that ZEB1 is a target of miR-139-5p, of which TTN-AS1 could regulate the expression through competition with miR-139-5p. That is, TTN-AS1 promoted proliferation and invasion of breast cancer cells by interaction with the miR-139-5p/ZEB1 axis. In conclusion, the present study aimed to illustrate the significance of TTN-AS1 in breast cancer metastasis and contribute to potentially innovative strategies for its treatment.

Long non-coding RNA OIP5-AS1 serves as an oncogene in laryngeal squamous cell carcinoma by regulating miR-204-5p/ZEB1 axis.

Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer with poor prognosis. In the present study, we aimed to investigate the biological role of long non-coding RNA OIP5-AS1 in LSCC. The results demonstrated that the expression levelsof OIP5-AS1 weresignificantly increased in LSCC tissues and cell lines. High expression of OIP5-AS1 was closely correlated with lymph node metastasis and advancedclinical stage of LSCC patients. Moreover, in vitro assays showed that OIP5-AS1 overexpression promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of LSCC cells, whereas OIP5-AS1 knockdown exerted suppressive effects on LSCC cells. Furthermore, OIP5-AS1 was confirmed to serve as a competing endogenous RNA of miR-204-5p in LSCC cells, and restoration of miR-204-5p counteracted the OIP5-AS1-mediated oncogenic effects. In conclusion, our study provides promising evidence that lncRNA OIP5-AS1 functions as a tumor promoter in LSCC and may be used as a potential target for LSCC therapy.

LncRNA PCAT6 Accelerates the Progression and Chemoresistance of Cervical Cancer Through Up-Regulating ZEB1 by Sponging miR-543.

BackgroundCervical cancer (CC) is a common cancer with a poor prognosis due to the chemoresistance of CC cells to cisplatin. This study aimed to investigate the biological significance of lncRNA prostate cancer-associated transcript 6 (PCAT6) in the carcinogenesis of CC.Materials and MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was carried out to measure the abundance of PCAT6, miR-543 and zinc finger E-box binding protein 1 (ZEB1) in CC tissues and cells. The combination between miR-543 and lncRNA PCAT6 or ZEB1 was predicted by Starbase and was verified by dual-luciferase reporter assay, RNA-pull down assay and RNA immunoprecipitation (RIP) assay. Cell proliferation and chemoresistance to cisplatin were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis and metastasis were determined by flow cytometry, Western blot and transwell migration and invasion assays.ResultsThe abundance of ZEB1 protein was measured by Western blot assay. Murine xenograft model was established to confirm the function of lncRNA PCAT6 in vivo. The abundance of lncRNA PCAT6 was enhanced in CC tissues and cells compared with that in corresponding normal tissues and normal cervical epithelial cells Ect1/E6E7. MiR-543 was a target of PCAT6 and was negatively regulated by PCAT6. PCAT6 accelerated the proliferation, metastasis and the chemoresistance of CC cells to cisplatin while suppressed the apoptosis of CC cells. The overexpression of PCAT6 reversed the inhibitory effects of miR-543 accumulation on the proliferation, metastasis and chemoresistance of CC cells to cisplatin and the promoting impact on the apoptosis of CC cells. ZEB1 was a direct target of miR-543, and it functioned as the downstream gene of PCAT6/miR-543 to exert its oncogenic role in CC. PCAT6 promoted the growth of murine xenograft tumor through miR-543/ZEB1 axis in vivo.ConclusionLncRNA PCAT6 facilitated the proliferation, metastasis and chemoresistance of CC cells to cisplatin while impeded the apoptosis of CC cells via PCAT6/miR-543/ZEB1 axis. PCAT6/miR-543/ZEB1 axis might be a promising target for CC therapy.

Long non-coding RNA HOTAIRM1 promotes proliferation and inhibits apoptosis of glioma cells by regulating the miR-873-5p/ZEB2 axis.

BackgroundGlioblastoma is one of the most common malignant brain tumors. Conventional clinical treatment of glioblastoma is not sufficient, and the molecular mechanism underlying the initiation and development of this disease remains unclear. Our study aimed to explore the expression and function of miR-873a-5p in glioblastoma and related molecular mechanism.MethodsWe analyzed the most dysregulated microRNAs from the Gene Expression Omnibus (GEO) database and examined the expression of miR-873-5p in 20 glioblastoma tissues compared with ten normal brain tissues collected in the Zhejiang Tongde Hospital. We then overexpressed or inhibited miR-873-5p expression in U87 glioblastoma cell lines and analyzed the phenotype using the cell counting kit-8 assay, wound healing assay, and apoptosis. In addition, we predicted upstream and downstream genes of miR-873-5p in glioblastoma using bioinformatics analysis and tested our hypothesis in U87 cells using the luciferase reporter gene assay and Western blotting assay. The differences between two groups were analyzed by Student's t test. The Kruskal-Wallis test was used for the comparison of multiple groups. A P < 0.05 was considered to be significant.ResultsThe miR-873-5p was downregulated in glioblastoma tissues compared with that in normal brain tissues (normal vs. tumor, 0.762 ± 0.231 vs. 0.378 ± 0.114, t = 4.540, P < 0.01). Overexpression of miR-873-5p inhibited cell growth (t = 6.095, P < 0.01) and migration (t = 3.142, P < 0.01) and promoted cell apoptosis (t = 4.861, P < 0.01), while inhibition of miR-873-5p had the opposite effect. Mechanistically, the long non-coding RNA HOTAIRM1 was found to act as a sponge of miR-873-5p to activate ZEB2 expression in U87 cells.ConclusionsWe uncovered a novel HOTAIRM1/miR-873-5p/ZEB2 axis in glioblastoma cells, providing new insight into glioblastoma progression and a theoretical basis for the treatment of glioblastoma.

Retracted Article: Circular RNA PTK2 modifies the progression and radiosensitivity in gastric cancer via miR-369-3p/ZEB1 axis.

Gastric cancer (GC) is one of the common cancers worldwide. Emerging findings imply that aberrant expression of circular RNA_0003221 (circPTK2) is involved in GC. Nevertheless, the function of circPTK2 in GC needs more explanation. Profiles of circPTK2, microRNA (miR)-369-3p, and zinc finger E-box binding homeobox 1 (ZEB1) were determined by quantitative real-time polymerase chain reaction assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were employed to estimate cell proliferation, apoptosis, and mobility in GC cells, respectively. Meanwhile, levels of ZEB1 and other indicated proteins were tested using western blot. Survival fraction was assessed utilizing clonogenic assay. Additionally, the role of circPTK2 in tumorigenesis was investigated via a xenograft tumor model. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were conducted to confirm the interrelation between miR-369-3p and circPTK2 or ZEB1. Levels of circPTK2 and ZEB1 were markedly augmented, but miR-369-3p was downregulated in GC tissues and cells. CircPTK2 depletion restrained cell growth, metastasis, and epithelial–mesenchymal transition, and promoted radiosensitivity in GC cells. And circPTK2 depletion reduced tumor growth and metastasis in vivo. Moreover, the effect of circPTK2 silencing on cellular phenotypes and radiosensitivity was regained by miR-369-3p inhibitor. Furthermore, upregulation of ZEB1 could overturn miR-369-3p mimic-induced effect on cell metastasis and radiosensitivity of GC cells. Mechanically, circPTK2 was a sponge of miR-369-3p to separate ZEB1. CircPTK2/miR-369-3p/ZEB1 axis modulated cell behaviors and radiosensitivity in GC; thus circPTK2 might serve as a promising target for GC therapy.

CircZFR serves as a prognostic marker to promote bladder cancer progression by regulating miR-377/ZEB2 signaling.

Circular RNAs (circRNAs) have been identified as crucial regulators of gene expression in human cancer biology. CircZFR is a novel identified circRNA and its effect in bladder cancer remains unclearly. In the present study, we aimed to investigate the role of circZFR in the progression of bladder cancer. First, we demonstrated that the expression of circZFR was higher in bladder cancer tissues and cells compared with adjacent non-tumor tissues and normal bladder epithelial cells. And higher circZFR levels were positively correlated with bladder cancer patients’ pathological T stage, grade, lymphatic metastasis, recurrence, progression-free survival (PFS) and overall survival (OS). Functionally, knockdown of circZFR could significantly prohibit cell growth, migration and invasion, arrest cell cycle as well as promote apoptosis of bladder cancer cells in vitro study. Mechanistically, we observed that circZFR could directly bind to miR-377 as sponge to promote ZEB2 expression in bladder cancer cells. In addition, rescue assays demonstrated that restoration of ZEB2 significantly impaired the suppressive effects of circZFR silencing on bladder cancer cells growth, migration and invasion. Taken together, our results illuminated that circZFR could be a prognostic biomarker in bladder cancer and exerted oncogenic roles through regulating miR-377/ZEB2 axis in bladder cancer, which indicated that circZFR could be a potential therapeutic target for bladder cancer patients treatment.

LncRNA SNHG5 Promotes Proliferation of Glioma by Regulating miR-205-5p/ZEB2 Axis.

BackgroundGlioma is a common primary brain tumor with extremely poor prognosis outcomes. Increasing evidences have proved the relation between lncRNAs and glioma onset and progression. LncRNA SNHG5 involves in the biological activities of tumor cells, such as proliferation, migration and metastasis. Nevertheless, it is still necessary to explain the molecular mechanism and biofunction of SNHG5 in glioma.Materials and methodsQuantitative real-time PCR (qRT-PCR) was performed to analyze expressions of SNHG5, miR-205-5p and ZEB2 in tumor tissues and cell lines. The cell counting kit-8 (CCK-8) assay, plate and soft agar colony formation assays were performed to evaluate cell proliferation ability. RNA immunoprecipitation assay and dual-luciferase reporter assay were used to confirm the interaction among SNHG5, miR-205-5p and ZEB2. The protein level of ZEB2 was measured by Western blot.ResultsBased on our findings, compared with normal tissues, the elevated expression of SNHG5 and decreased expression of miR-205-5p were observed in glioma tissues. The downregulation of SNHG5 exerted an obvious inhibitory effect on glioma cells in terms of their proliferation. With regard to the underlying mechanism, SNHG5 presented a direct inhibitory influence on miR-205-5p which targeted to the 3′-UTR region of zinc finger E-box binding homeobox 2 (ZEB2) mRNA. As a competing endogenous RNA (ceRNA), SNHG5 sponged miR-205-5p, regulating the expression of ZEB2 thereby.ConclusionThese discoveries indicate that SNHG5 promotes proliferation of glioma by regulating miR-205-5p/ZEB2 axis.

RETRACTED ARTICLE: LncRNA MINCR regulates irradiation resistance in nasopharyngeal carcinoma cells via the microRNA-223/ZEB1 axis

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Qingmu Zhong, Yifeng Chen, and Zilong Chen. LncRNA MINCR regulates irradiation resistance in nasopharyngeal carcinoma cells via the microRNA-223/ZEB1 axis. Cell Cycle. 2020;19(1):53-66. doi: 10.1080/15384101.2019.1692176. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to provide their original data or sufficient supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted.’

LncRNA TDRG1 promotes the metastasis of NSCLC cell through regulating miR-873-5p/ZEB1 axis.

Long noncoding RNAs (lncRNAs) are dysregulated in various malignancies and involved in the growth and aggressive phenotypes of cancer cells. Previous studies indicate that lncRNA testis development related 1 (TDRG1) plays critical roles in the development of several malignancies. Nevertheless, the molecular mechanism underlying TDRG1 contributes to non-small cell lung cancer (NSCLC) remains elusive. Here, we demonstrate that TDRG1 is significantly overregulated in NSCLC tissues and cell lines. Knockdown of TDRG1 inhibits the proliferation and metastatic-related traits of NSCLC cell in vitro whereas overexpression of TDRG1 causes opposite results. In addition, TDRG1 silencing inhibits the growth and metastatic ability of NSCLC cell in vivo as demonstrated by xenograft tumor model and lung metastasis model. The binding capacity of TDRG1 with miR-873-5p is demonstrated by bioinformatics prediction tool and luciferase reporter gene assay. Additional, the rescue experiments indicate that TDRG1 interacts with miR-873-5p and its expression is positively associated with the target of miR-873-5p, zinc finger e-box binding homeobox 1 (ZEB1). Altogether, lncRNA TDRG1 facilitates the progression of NSCLC via interacting with miR-873-5p and positively regulates the expression of ZEB1.

Targeting ZEB2 By microRNA-129 In Non-Small Cell Lung Cancer Suppresses Cell Proliferation, Invasion And Migration Via Regulating Wnt/β-Catenin Signaling Pathway And Epithelial-Mesenchymal Transition.

IntroductionNon-small cell lung cancer (NSCLC) is a common cause of deaths all over the world. Emerging evidence has indicated that microRNA (miR) play key roles in NSCLC progression. We aimed to determine the functions of miR-129 in NSCLC. miR-129 was dramatically downregulated in NSCLC tissue samples and cells. The decreased miR-129 was found to be associated with poorer prognosis and malefic phenotype of NSCLC patients. We demonstrated that miR-129 upregulation could inhibit NSCLC cell growth. Furthermore, we also sought the molecular mechanism by which miR-129 repressed NSCLC development.MethodsQRT-PCR was applied to detect the expressions of miR-129 in 51 pairs of NSCLC tissue samples. We further performed the Kaplan–Meier analysis to determine the association between miR-129 expressions and the survival rate of NSCLC patients. We then measured the expression levels of miR-129 in NSCLC cell lines. After that, MTT assays were performed to determine the influence of miR-129 on A549 cell proliferation. Transwell assay was then conducted to explore the biological functions of miR-129 in invasion and migration of NSCLC cells.ResultsResults showed that ZEB2 was directly targeted by miR-129 in NSCLC cell lines. Moreover, miR-129 restoration could inhibit EMT and Wnt/β-catenin in NSCLC cell lines.ConclusionIn short, all these results indicated that miR-129/ZEB2 axis maybe a useful diagnostic and prognostic biomarker for NSCLC treatment.

MicroRNA-1236-3p inhibits proliferation and invasion of breast cancer cells by targeting ZEB1.

This research aims to investigate the level of microRNA-1236-3p in breast cancer (BCa) tissues and to further investigate its possible mechanism in the progression of BCa. The level of microRNA-1236-3p in BCa tissues and adjacent tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Regulatory effects of microRNA-1236-3p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) and transwell assay. The binding relationship between microRNA-1236-3p and zinc-finger E-box binding homeobox (ZEB1) was examined by the dual-luciferase reporter gene assay. Finally, rescue experiments were conducted to verify the potential role of microRNA-1236-3p/ ZEB1 axis in BCa. MicroRNA-1236-3p was downregulated in BCa tissues relative to adjacent tissues, and the similar trend was shown in BCa cell lines. Overexpression of microRNA-1236-3p in MDA-MB-231 and MCF-7 cells inhibited proliferation and attenuated invasiveness, while knockdown of microRNA-1236-3p had an opposite effect. Dual-luciferase reporter gene assay and qRT-PCR results showed that microRNA-1236-3p could target ZEB1 to degrade it. Overexpression of ZEB1 in BCa cells can partially reverse the effect of overexpressed miR-1236-3p on cell proliferative and invasive abilities. MicroRNA-1236-3p could inhibit the growth and metastasis of BCa cells by inhibiting ZEB1 expression, suggesting that microRNA-1236-3p may be a potential therapeutic target for BCa.

LncRNA-CTS promotes metastasis and epithelial-to-mesenchymal transition through regulating miR-505/ZEB2 axis in cervical cancer.

Cervical carcinoma (CC) is the second most common cancer in females. In order to improve current anti-metastasis strategies for CC, it is important to improve our understanding of the mechanisms involved in epithelial-to-mesenchymal transition (EMT). This study aimed to elucidate the potential role of a novel long non-coding RNA (lncRNA)-CTS and the mechanisms underlying EMT in CC. The expression levels of lncRNA-CTS and miR-505 were detected using quantitative reverse transcriptase polymerase chain reaction in CC specimens and cells (HeLa, SiHa, Ca-Ski, C-33A, and HT-3). Further experiments including wound scratch and transwell invasion assays, Western blotting, immunofluorescence, and luciferase assays were used to investigate the function of lncRNA-CTS/miR-505/ZEB2 in vitro. In addition, a tumor xenograft model was used to assess the effect of lncRNA-CTS in vivo. The expression levels of lncRNA-CTS and miR-505 were correlated with the metastasis-associated clinicopathological features of CC patients. Moreover, lncRNA-CTS was associated with a poor prognosis in CC patients. In vitro and in vivo experiments, along with gain- and loss-of-function studies, showed that lncRNA-CTS enhanced cell migration, invasion, and the transforming growth factor (TGF)-β1-induced-EMT process. Data also showed that lncRNA-CTS could function as a competing endogenous RNA for miR-505 in CC cells. Further investigations disclosed that ZEB2 was demonstrated as a downstream target of miR-505, and subsequently exerted its metastatic effects via the lncRNA-CTS/miR-505/ZEB2 axis in CC cells. Finally, lncRNA-CTS activated the SMAD/TGF pathway via miR-505 in CC cells. Collectively, our results demonstrate the importance of the lncRNA-CTS/miR-505/ZEB2 axis in CC. LncRNA-CTS can predispose CC patients to metastases and may represent a promising therapeutic target for CC.

466 OVO-like2/ZEB1 axis inhibits a promotion of actinic keratosis towards squamous cell carcinoma

466 OVO-like2/ZEB1 axis inhibits a promotion of actinic keratosis towards squamous cell carcinoma

MiR-1271 inhibits growth, invasion and epithelial-mesenchymal transition by targeting ZEB1 in ovarian cancer cells.

ObjectiveMicroRNA-1271 (miR-1271) has a role in suppressing cell growth, cell cycle and promoting cell apoptosis in many cancers. This research was to explore the great role of miR-1271 in ovarian cancer (OC).Patients and MethodsRT-qPCR was utilized to evaluate the mRNA levels of miR-1271 and its target gene. The proliferative and invasive abilities were measured using Cell Counting Kit-8 and transwell assays. The overall survival rate of OC patients was assessed by Kaplan–Meier method.ResultsmiR-1271 was downregulated in OC tissues, and downregulation of miR-1271 predicted a poor outcome of the OC patients. Zinc finger E-box binding homeobox 1 (ZEB1) was a target gene of miR-1271 and its expression was regulated by miR-1271 in OC. The expression of miR-1271 had a negative connection with the expression of ZEB1 in OC tissues. miR-1271 inhibited cell viability and invasion-mediated epithelial–mesenchymal transition in SKOV3 cells. ZEB1 reversed partial roles of miR-1271 on viability and invasion in OC.ConclusionmiR-1271 inhibited cell proliferation and invasion-mediated EMT in OC. The newly identified miR-1271/ZEB1 axis provides novel insight into the pathogenesis of OC.

PCAT-1 contributes to cisplatin resistance in gastric cancer through miR-128/ZEB1 axis

Increasing evidence suggests that dysregulation of long non-coding RNAs (lncRNAs) is implicated with chemoresistance in cancers. However, their function and molecular mechanisms in gastric cancer (GC) chemoresistance remain not well elucidated. In this study, we aimed to investigate the functional role and the underlying molecular mechanism of lncRNA prostate cancer-associated transcript 1 (PCAT-1) in cisplatin (DDP) resistance of GC. Our results revealed that PCAT-1 was up-regulated in DDP-resistant GC tissues and cells. GC patients with high PCAT-1 expression levels had a poor prognosis. Knockdown of PCAT-1 facilitated the sensitivity of DDP-resistant GC cells to DDP. Additionally, PCAT-1 functioned as a sponge of miR-128 in GC cells. Moreover, inhibition of miR-128 reversed the inductive effect of PCAT-1 knockdown on DDP sensitivity of GC cells. In addition, ZEB1 was identified as a target of miR-128, and overexpression of ZEB1 could block the inductive effect of PCAT-1 knockdown on DDP sensitivity of GC cells. Besides, PCAT-1 knockdown enhanced DDP sensitivity in tumors in vivo. In summary, PCAT-1 confers DDP resistance in GC cells through miR-128/ZEB1 axis, providing a promising therapeutic strategy for GC.

LncRNA TTN‐AS1 drives invasion and migration of lung adenocarcinoma cells via modulation of miR‐4677‐3p/ZEB1 axis

Lung adenocarcinoma is the most prevalent type of lung cancer with a high incidence and mortality worldwide. Metastasis is the major cause of high death rate in lung cancer and the potential mechanism of lung adenocarcinoma metastasis remains indistinct. Emerging investigations have demonstrated that long noncoding RNA is a kind of non-protein coding RNA and plays a critical role in cancer progression and metastasis. TTN antisense RNA 1 (TTN-AS1) has been reported to promote cell growth and metastasis in cancer. However, the function of TTN-AS1 in lung adenocarcinoma is still to be illustrated. In this study, we observed that TTN-AS1 was upregulated in tissues and cells of lung adenocarcinoma and associated with poor overall survival. TTN-AS1 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition in lung cancer. TTN-AS1 directly bound with miR-4677-3p and negatively regulated miR-4677-3p. MiR-4677-3p rescued the inhibitive impacts of TTN-AS1 knockdown on lung adenocarcinoma. Furthermore, zinc finger E-box binding homeobox 1 (ZEB1) was the target of miR-4677-3p, and TTN-AS1 modulated ZEB1 by competing for miR-4677-3p. TTN-AS1 drove the invasion and migration of lung adenocarcinoma cells by targeting the miR-4677-3p/ZEB1 axis. To sum up, our study offers insights into the mechanism of TTN-AS1 in lung adenocarcinoma metastasis and targeting the TTN-AS1/miR-4677-3p/ZEB1 axis may be the potential innovate therapeutic strategy for the patients with lung adenocarcinoma.

Long non-coding RNA SPRY4-IT1 promotes epithelial-mesenchymal transition of cervical cancer by regulating the miR-101-3p/ZEB1 axis.

Background: Emerging evidences have indicated that long non-coding RNAs (LncRNAs) play vital roles in cancer development and progression. Previous studies have suggested that overexpression of SPRY4 intronic transcript 1 (SPRY4-IT1) predicates poor prognosis and promotes tumor progress in cervical cancer (CC). However, the underlying mechanism of SPRY4-IT1 in CC remains unknown. The aim of the present study is to evaluate the function and mechanism of SPRY4-IT1 in CC.Methods: SPRY4-IT1 was detected by quantitative PCR. Wound-healing assay and Transwell assay were performed to detect cell migration and invasion, respectively. Western blotting assays were used to analyze the protein expression of E-cadherin, N-cadherin and vimentin. Tumor xenografts experiments were performed to detect the effect of SPRY4-IT1 in vivo. Dual luciferase reporter assay was used to investigate potential molecular mechanism of SPRY4-IT1 in CC cells.Results: SPRY4-IT1 was up-regulated in CC cell lines. Knockdown of SPRY4-IT1 significantly inhibited CC cells migration and invasion in vitro and in vivo. Moreover, knockdown of SPRY4-IT1 significantly suppressed the epithelial–mesenchymal transition (EMT) of CC by increased E-cadherin expression and decreased the N-cadherin and vimentin expression. Mechanically, SPRY4-IT1 could directly bind to miR-101-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-101-3p to regulate the expression of the target gene ZEB1.Conclusions: Our findings indicate that the SPYR4-IT1/miR-101-3p/ZEB1 axis contributes to CC migration and invasion, which may provide novel insights into the function of lncRNA-driven tumorigenesis of CC.